Mitochondrial redox state as a potential detector of liver dysoxia in vivo.
Dysoxia can be defined as ATP flux decreasing in proportion to O2 availability with preserved ATP demand. Hepatic venous beta-hydroxybutyrate-to-acetoacetate ratio (beta-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detect the onset of dysoxia. During partial dysoxia (as opposed to anoxia), however, flow may be adequate in some liver regions, diluting effluent from dysoxic regions, thereby rendering venous beta-OHB/AcAc unreliable. To address this concern, we estimated tissue ATP while gradually reducing liver blood flow of swine to zero in a nuclear magnetic resonance spectrometer. ATP flux decreasing with O2 availability was taken as O2 uptake (VO2) decreasing in proportion to O2 delivery (QO2); and preserved ATP demand was taken as increasing Pi/ATP. VO2, tissue Pi/ATP, and venous beta-OHB/AcAc were plotted against QO2 to identify critical inflection points. Tissue dysoxia required mean QO2 for the group to be critical for both VO2 and for Pi/ATP. Critical QO2 values for VO2 and Pi/ATP of 4.07 +/- 1.07 and 2.39 +/- 1.18 (SE) ml . 100 g-1 . min-1, respectively, were not statistically significantly different but not clearly the same, suggesting the possibility that dysoxia might have commenced after VO2 began decreasing, i.e., that there could have been "O2 conformity." Critical QO2 for venous beta-OHB/AcAc was 2.44 +/- 0.46 ml . 100 g-1 . min-1 (P = NS), nearly the same as that for Pi/ATP, supporting venous beta-OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector of dysoxia in liver.
Dishart
M K
MK
Department of Research and Development, Veterans Affairs Medical Center, Pittsburgh 15240, USA.
Schlichtig
R
R
Tonnessen
T I
TI
Rozenfeld
R A
RA
Simplaceanu
E
E
Williams
D
D
Gayowski
T J
TJ
D000090:Acetoacetates / Q000097:blood; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008102:Liver Circulation / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D012978:Sodium Oxybate / Q000097:blood; D013552:Swine
D000090:Acetoacetates; D009243:NAD; C016635:acetoacetic acid; D012978:Sodium Oxybate; D000255:Adenosine Triphosphate